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Progabide ( INN; trade name Gabrene, Sanofi-Aventis) is an analogue and
prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the GABAA, GABAB, and GABAA-ρ receptors.
Uses
Progabide is approved in France for either monotherapy or adjunctive use in the treatment of epilepsy—specifically, generalized tonic-clonic, myoclonic, partial, and Lennox-Gastaut syndrome seizures—in both children and adults. Progabide has been investigated for many diseases besides epilepsy, including Parkinson's disease, schizophrenia, clinical depression,anxiety disorder
Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
and spasticity with various levels of success.
In 1987, Bartolini and colleagues reported progabide's actions on dopamine to be contradictory, decreasing dopamine release, dopamine receptor density and postsynaptic receptor responsivity to dopamine while reducing striatal cholinergic activity so as to increase dopaminergic effects. Bartholini and colleagues concluded that it was this that caused Parkinson's patients in human clinical trials to either see an improvement in their Parkinson's with a worsening of L-dopa dyskinesia or an improvement in dyskinesia but with sometimes aggravated Parkinson's symptoms. The cholinergic effect takes only a single injection to achieve in rats; when given with haloperidol, the development of tolerance to haloperidol's cataleptic effects did not develop. It was hoped that this would be effective for tardive dyskinesia. However, Soares, Rathbone and Deeks wrote in the 2004 issue of ''The Cochrane Database of Systematic Reviews'' that "Any possible benefits are likely to be outweighed by the adverse effects associated with their ABAergic agents'use."
In addition to being tested for antipsychotic-induced tardive dyskinesia, progabide was itself tested as an antipsychotic; as early as 1979, it was obvious that it was ineffective for psychosis. (French) While progabide may have been devoid of antipsychotic effects, it did have the effect in schizoaffective and hebephrenic patients of improving environmental responsiveness and social interactions.
Synthesis
See also
*Progabide acid
SL-75102, or progabide acid, is an active metabolite of progabide and an anticonvulsant GABA receptor agonist
A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, an ...
(SL-75102), an active metabolite of progabide
* Tolgabide
Tolgabide (INN; development code SL-81.0142) is a drug which was patented by Synthélabo as an anticonvulsant but was never marketed. It is an analogue of progabide and acts similarly to it as a prodrug of GABA, and therefore as an indirect ...
References
{{GABAergics Anticonvulsants Chlorobenzenes GABA analogues GABAA receptor agonists GABAA-rho receptor agonists GABAB receptor agonists Fluoroarenes Phenols Imines